TIS for Brain Network Modulation and Clinical Efficacy in Parkinson's Disease (PD TIS)

Jiangsu Province Nanjing Brain Hospital

Status

Not yet enrolling

Conditions

PARKINSON DISEASE (Disorder)

Treatments

Device: Temporal Interference Stimulation (130 Hz)

Device: Sham Temporal Interference Stimulation

Device: Temporal Interference Stimulation (40 Hz)

Study type

Interventional

Funder types

Other

Identifiers

NCT07480317

2026-KY020-01

Details and patient eligibility

About

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. While deep brain stimulation (DBS) is effective, its invasive nature limits its application in early-stage patients. Temporal interference stimulation (TIS) is a novel non-invasive technique that can target deep brain structures like the globus pallidus internus (GPi) by using high-frequency electric fields.

This study aims to evaluate the clinical value and underlying mechanisms of TIS in PD patients. The research is divided into two phases: Phase A investigates the immediate regulatory effects of 130 Hz and 40 Hz TIS on brain networks using concurrent fMRI-TIS. Phase B is a randomized, double-blind, sham-controlled trial to assess the long-term efficacy and safety of a 2-week TIS intervention on both motor and non-motor symptoms. The results will help clarify how TIS modulates deep brain networks and its potential as a non-invasive therapy for PD.

Full description

This study employs a two-phase design to systematically investigate the effects of Temporal Interference Stimulation (TIS) on Parkinson's Disease (PD).

Phase A: Acute fMRI Mechanism Study (n=15) In this crossover study, participants will undergo concurrent fMRI-TIS sessions. Two frequency envelopes will be tested: 130 Hz (to mimic DBS inhibitory effects) and 40 Hz (for gamma entrainment). The fMRI protocol follows an 8-20-8 minute design: 8 minutes of baseline, 20 minutes of concurrent stimulation, and 8 minutes of post-stimulation scan . Individualized electric field modeling based on high-resolution 3D-T1 MRI will be used to target the right GPi. Acute motor changes will be assessed using the MDS-UPDRS-III scale.

Phase B: Long-term Efficacy RCT (n=60) Participants will be randomly assigned to one of three parallel groups: 130 Hz TIS, 40 Hz TIS, or Sham stimulation. The intervention consists of 30-minute daily sessions for 2 weeks (10 sessions total).

Active Groups: TIS targeting the right GPi with individualized electrode configurations.

Sham Group: 20-second ramp-up and ramp-down to mimic skin sensation without continuous stimulation.

Clinical assessments including motor function (MDS-UPDRS), cognition (MoCA), mood (HAMD/HAMA), and sleep (PDSS-2) will be conducted at baseline, after the 2-week intervention, and at a 1-month follow-up . Long-term neuroplasticity will also be evaluated using multi-modal MRI post-intervention.

Enrollment

75 estimated patients

Sex

All

Ages

45 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosed with Parkinson's Disease according to the Movement Disorder Society (MDS) clinical diagnostic criteria.
Hoehn & Yahr Stage I-III (mild to moderate severity).
Aged 45 to 65 years.
Right-handed. Stable medication regimen for at least 1 hour before Phase A fMRI sessions and agreement to maintain a stable dosage during the 2-week Phase B intervention (unless clinically necessary).
Able to provide informed consent by the participant or a legal guardian.

Exclusion criteria

MRI contraindications, such as implanted DBS electrodes, cardiac pacemakers, or other metal implants.
Significant cognitive impairment (MoCA score < 24) or severe psychiatric symptoms.
History of epilepsy or structural brain lesions, including severe cerebral atrophy or cerebrovascular disease.
Severe head tremors that would interfere with MRI scanning quality.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

75 participants in 3 patient groups

130 Hz TIS Group

Experimental group

Description:

Participants receive active Temporal Interference Stimulation (TIS) with a 130 Hz envelope frequency targeting the right globus pallidus internus (GPi).

Treatment:

Device: Temporal Interference Stimulation (130 Hz)

40 Hz TIS Group

Experimental group

Description:

Participants receive active TIS with a 40 Hz envelope frequency targeting the right GPi.

Treatment:

Device: Temporal Interference Stimulation (40 Hz)

Sham Group

Sham Comparator group

Description:

Participants receive sham stimulation targeting the right GPi.